Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,de...Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.展开更多
In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units an...In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stifness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stifness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stifness fully decoupled 3T PM. Kinematic and stifness analyses show that the Jacobian matrix is a diagonal matrix, and the stifness is obviously higher than that of the coupling mechanisms, which verifes the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.展开更多
Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Da...Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integration methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.展开更多
Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment c...Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.展开更多
The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantati...The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.展开更多
Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of s...Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.展开更多
目的作为一本新创的英文期刊,Journal of Translational Neuroscience杂志需要尽快提升其学术水平,扩大其社会影响力,以期能迅速在国际专业学术期刊界占有一席之地,通过约稿获得高质量的学术论文就显得至关重要。方法笔者从找准期刊学...目的作为一本新创的英文期刊,Journal of Translational Neuroscience杂志需要尽快提升其学术水平,扩大其社会影响力,以期能迅速在国际专业学术期刊界占有一席之地,通过约稿获得高质量的学术论文就显得至关重要。方法笔者从找准期刊学术定位、采取灵活多样的约稿方式、分析解决约稿过程中可能存在的问题以及如何做好约稿后续服务工作等几个方面入手,初浅分析探讨了关于期刊约稿的方式方法。结果通过期刊定位准确锁定目标作者群,依托自身优势资源,参与学术会议,通过编委约稿以及提供优质的后续服务等方法获得稳定的高质量作者群,从而获得持续的优秀稿源。结论拥有持续的高质量稿件是促使期刊进入良性循环的重要保障,通过约稿可以解决新创办的期刊无稿可用和缺少优秀稿件的难题,推动期刊走出困境,渐入正轨。展开更多
Spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as...Spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as a global medical challenge for many years.Significant progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction.展开更多
Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti...Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti-diabetic and anti-cancer properties, cinnamon also exerts strong brain protective and pro-cogrdtive effects in various models of neurodegeneration (Kawatra et al., 2015;Kelestemur et al., 2016)(Figure 1).展开更多
Coupling is the significant characteristic of parallel mechanism,while it is just the coupling that brings about much difficulty for the configuration design,theoretical analysis and the development of the control sys...Coupling is the significant characteristic of parallel mechanism,while it is just the coupling that brings about much difficulty for the configuration design,theoretical analysis and the development of the control system of the parallel mechanism. And recently,the research on the decoupled parallel mechanism becomes one of the research hot points in the mechanism fields. In this paper,a type synthesis method for the translational decoupled parallel mechanism( TDPM) is proposed based on the screw theory. To achieve the decoupling characteristics of the translational parallel mechanism,the translational decoupled criterion for type synthesis of the branches are presented in this paper. According to this criterion and the realization conditions of rotational degree of freedom of the mechanism proposed former,a large number of branches for the TDPM are obtained. Taking the three degrees of freedom( DOFs) TDPM as an example,the process of type synthesis is discussed in detail. Using this proposed type synthesis method,a serial of translational decoupled parallel mechanisms, including but not limited to all the existing typical 3-DOF TDPMs, are obtained, which identifies the correctness and effective of the method. The contents of this paper provide a reference and possess significant theoretical meanings for the synthesis and development of the novel decoupled parallel mechanisms.展开更多
The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbe...The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.展开更多
Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELON...Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELONGATED HYPOCOTYL 5(HY5),a master regulator in the light signaling pathway,is required for normal fruit ripening in tomato(Solanum lycopersicum).Loss of function of tomato HY5(SlHY5)impairs pigment accumulation and ethylene biosynthesis.Transcriptome profiling identified 2948 differentially expressed genes,which included 1424 downregulated and 1524 upregulated genes,in the Slhy5 mutants.In addition,genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation.Surprisingly,the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants,and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins.Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes.These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery.Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.展开更多
Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e....Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.展开更多
Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model...Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.展开更多
The structural evolution fromβ_(1)(Mg_(3)Ce)toβ(Mg_(12)Ce)precipitates,which takes place at the over-aged stage of binary Mg-Ce alloys,are investigated by high-angle annular dark-field scanning transmission electron...The structural evolution fromβ_(1)(Mg_(3)Ce)toβ(Mg_(12)Ce)precipitates,which takes place at the over-aged stage of binary Mg-Ce alloys,are investigated by high-angle annular dark-field scanning transmission electron microscopy.The structural transformation mainly occurs in the{111}_(β1)crystallographic planes,where the newly formedβlattices exhibit two categories of domain structures,namely rotational and translational domains.The rotational domain is composed of threeβdomains(β_(RA),β_(RB)andβ_(RC)),which are related by a 120°rotation with respect to each other around the 111_(β1)axis of theirβ_(1)parent phase.The{111}_(β1)crystallographic planes can provide four sets of sublattices with the same orientation for an initial nucleation ofβlattice.It leads to the formation of four translationalβdomains(β_(TA),β_(TB),β_(TC)andβ_(TD)),among which any two differ by a vector of 1/6112_(β1).We deduce theoretically that there exist twenty-fourβdomains during this transition.However,considering the interfacial misfit,only one-third of domains can grow up and eventually formsβribbon.Furthermore,a majority ofβribbons overlap partiallyβ_(1)plate,which is beneficial to relax interfacial strain amongβ,β_(1)andα-Mg matrix(α/β/β_(1)).The configuration of multipleβdomains can effectively regulate interfacial misfit ofα/βandβ/β_(1),which are responsible for enhancing the hardness and strength of Mg-Ce alloy.Additionally,this study aims to provide some clues to improve the over-aged performance of magnesium alloys by constructingβdomains and optimizing theα/β/β_(1)interface.展开更多
Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceut...Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research.展开更多
Translational Chinese medicine is one of the latest developing fields in traditional Chinese medicine. In this paper, we discuss the “3 w” namely, “what is”, “why to advance”, “how to carry out” and the signif...Translational Chinese medicine is one of the latest developing fields in traditional Chinese medicine. In this paper, we discuss the “3 w” namely, “what is”, “why to advance”, “how to carry out” and the significance of translational Chinese medicine. To overcome the innate drawbacks of traditional Chinese medicine (TCM), the basic theory of TCM had better be refreshed. The safety and efficacy of classic formulae and therapy experience of TCM should be evaluated based on strict quality control and reaffirmed with evidence based medicine. The significance of translational Chinese medicine is to transform Chinese medicine into a balanced, personalized medicine with sound safety, good efficacy and strict quality control.展开更多
In a dynamic CT, the acquired projections are corrupted due to strong dynamic nature of the object, for example: lungs, heart etc. In this paper, we present fan-beam reconstruction algorithm without position-dependent...In a dynamic CT, the acquired projections are corrupted due to strong dynamic nature of the object, for example: lungs, heart etc. In this paper, we present fan-beam reconstruction algorithm without position-dependent backprojection weight which compensates for the time-dependent translational, uniform scaling and rotational deformations occurring in the object of interest during the data acquisition process. We shall also compare the computational cost of the proposed reconstruction algorithm with the existing one which has position-dependent weight. To accomplish the objective listed above, we first formulate admissibility conditions on deformations that is required to exactly reconstruct the object from acquired sequential deformed projections and then derive the reconstruction algorithm to compensate the above listed deformations satisfying the admissibility conditions. For this, 2-D time-dependent deformation model is incorporated in the fan-beam FBP reconstruction algorithm with no backprojection weight, assuming the motion parameters being known. Finally the proposed reconstruction algorithm is evaluated with the motion corrupted projection data simulated on the computer.展开更多
Sound pressure waves surround individuals in everyday life and are perceived by animals and humans primarily through sound or vibration. When sound pressure waves traverse through a solid medium, vibration will result...Sound pressure waves surround individuals in everyday life and are perceived by animals and humans primarily through sound or vibration. When sound pressure waves traverse through a solid medium, vibration will result. Vibration has long been considered an unwanted variable in animal research and may confound scientific endeavors using animals. Understanding the characteristics of vibration is required to determine whether effects in animals are likely to be therapeutic or result in adverse biological effects. The eighth edition of the "Guide for the Care and Use of Laboratory Animals" highlights the importance of considering vibration and its effects on animals in the research setting, but knowledge of the level of vibration for eliciting these effects was unknown. The literature provides information regarding therapeutic use of vibration in humans, but the range of conditions to be of therapeutic benefit is varied and without clarity. Understanding the characteristics of vibration(eg, frequency and magnitude) necessary to cause various effects will ultimately assist in the evaluation of this environmental factor and its role on a number of potential therapeutic regimens for use in humans. This paper will review the principles of vibration, sources within a research setting, comparative physiological effects in various species, and the relative potential use of vibration in the mouse as a translational research model.展开更多
As a major medical and scientific problem perplexing mankind,cardiovascular disease seriously endangers human health and life safety,which is still the primary cause of death.Traditional Chinese medicine(TCM)plays an ...As a major medical and scientific problem perplexing mankind,cardiovascular disease seriously endangers human health and life safety,which is still the primary cause of death.Traditional Chinese medicine(TCM)plays an irreplaceable role in the prevention and treatment of cardiovascular diseases and has its own characteristics and definite advantages.However,the unclear mechanism hinders its further promotion,which is not conducive to the prevention and treatment of cardiovascular diseases.Translational medicine advocates interdisciplinary integration and cooperation between academic groups,to establish effective interaction between basic research and clinical application,lead more medical research to focus on the prevention and treatment of clinical diseases,as well as to accelerate the transformation from“discovery”to“realization”,and finally to benefit patients,that is,“from clinic and serve clinic”.This provides a reference mode for the development and research direction of TCM,which comes from clinical practice originally.Based on this,considering the important role of angiogenesis in the occurrence and prognosis of cardiovascular diseases,under the guidance of the concept of translational medicine,this manuscript sorts out the overview of TCM treatment on angiogenesis related cardiovascular diseases from four aspects:theoretical basis,pathogenesis and pathology,applied prescriptions and material basis,in order to summarize the translational medicine experience of TCM prevention and treatment from clinical practice to modern research,to provide a basis for basic research and clinical diagnosis and treatment of related diseases.展开更多
基金supported by The Plastic Surgery Foundation Research Pilot Grant,No.627383(to KAS).
文摘Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.
基金Supported by National Natural Science Foundation of China(Grant No.52275032)Key Project of Hebei Provincial Natural Science Foundation of China(Grant No.E2022203077)Hebei Provincial Key Research and Development Plan of China(Grant No.202230808010057).
文摘In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stifness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stifness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stifness fully decoupled 3T PM. Kinematic and stifness analyses show that the Jacobian matrix is a diagonal matrix, and the stifness is obviously higher than that of the coupling mechanisms, which verifes the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.
基金supported by a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship(021207-00001)from Nanyang Technological University(NTU)Singapore and a Mistletoe Research Fellowship(022522-00001)from the Momental Foundation USA.Jialiu Zeng is supported by a Presidential Postdoctoral Fellowship(021229-00001)from NTU Singapore and an Open Fund Young Investigator Research Grant(OF-YIRG)(MOH-001147)from the National Medical Research Council(NMRC)SingaporeSu Bin Lim is supported by the National Research Foundation(NRF)of Korea(Grant Nos.:2020R1A6A1A03043539,2020M3A9D8037604,2022R1C1C1004756)a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(Grant No.:HR22C1734).
文摘Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integration methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.
文摘Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.
文摘The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.
文摘Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.
文摘目的作为一本新创的英文期刊,Journal of Translational Neuroscience杂志需要尽快提升其学术水平,扩大其社会影响力,以期能迅速在国际专业学术期刊界占有一席之地,通过约稿获得高质量的学术论文就显得至关重要。方法笔者从找准期刊学术定位、采取灵活多样的约稿方式、分析解决约稿过程中可能存在的问题以及如何做好约稿后续服务工作等几个方面入手,初浅分析探讨了关于期刊约稿的方式方法。结果通过期刊定位准确锁定目标作者群,依托自身优势资源,参与学术会议,通过编委约稿以及提供优质的后续服务等方法获得稳定的高质量作者群,从而获得持续的优秀稿源。结论拥有持续的高质量稿件是促使期刊进入良性循环的重要保障,通过约稿可以解决新创办的期刊无稿可用和缺少优秀稿件的难题,推动期刊走出困境,渐入正轨。
基金the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100).
文摘Spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as a global medical challenge for many years.Significant progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction.
文摘Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti-diabetic and anti-cancer properties, cinnamon also exerts strong brain protective and pro-cogrdtive effects in various models of neurodegeneration (Kawatra et al., 2015;Kelestemur et al., 2016)(Figure 1).
基金Sponsored by the National Natural Science Foundation of China(Grant No.51005195,51205339)
文摘Coupling is the significant characteristic of parallel mechanism,while it is just the coupling that brings about much difficulty for the configuration design,theoretical analysis and the development of the control system of the parallel mechanism. And recently,the research on the decoupled parallel mechanism becomes one of the research hot points in the mechanism fields. In this paper,a type synthesis method for the translational decoupled parallel mechanism( TDPM) is proposed based on the screw theory. To achieve the decoupling characteristics of the translational parallel mechanism,the translational decoupled criterion for type synthesis of the branches are presented in this paper. According to this criterion and the realization conditions of rotational degree of freedom of the mechanism proposed former,a large number of branches for the TDPM are obtained. Taking the three degrees of freedom( DOFs) TDPM as an example,the process of type synthesis is discussed in detail. Using this proposed type synthesis method,a serial of translational decoupled parallel mechanisms, including but not limited to all the existing typical 3-DOF TDPMs, are obtained, which identifies the correctness and effective of the method. The contents of this paper provide a reference and possess significant theoretical meanings for the synthesis and development of the novel decoupled parallel mechanisms.
文摘The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.
基金the National Natural Science Foundation of China(grant Nos.31801601,31925035,and 31871855)the China Postdoctoral Science Foundation(2018T110153)the Youth Innovation Promotion Association CAS(2019083).
文摘Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELONGATED HYPOCOTYL 5(HY5),a master regulator in the light signaling pathway,is required for normal fruit ripening in tomato(Solanum lycopersicum).Loss of function of tomato HY5(SlHY5)impairs pigment accumulation and ethylene biosynthesis.Transcriptome profiling identified 2948 differentially expressed genes,which included 1424 downregulated and 1524 upregulated genes,in the Slhy5 mutants.In addition,genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation.Surprisingly,the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants,and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins.Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes.These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery.Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.
基金funded by Ministry of Education,University and Research(MIUR)ex-60%research fund University of Brescia,Italy.Emilio Merlo Pich is employee of Takeda Pharmaceutical International AG
文摘Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.
基金supported by the start-up grant from“Top 100 Talents Program”of Sun Yat-sen University to JRY(50000-31131114)General Program of National Natural Science Foundation of China to JRY(31671320)
文摘Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.
文摘The structural evolution fromβ_(1)(Mg_(3)Ce)toβ(Mg_(12)Ce)precipitates,which takes place at the over-aged stage of binary Mg-Ce alloys,are investigated by high-angle annular dark-field scanning transmission electron microscopy.The structural transformation mainly occurs in the{111}_(β1)crystallographic planes,where the newly formedβlattices exhibit two categories of domain structures,namely rotational and translational domains.The rotational domain is composed of threeβdomains(β_(RA),β_(RB)andβ_(RC)),which are related by a 120°rotation with respect to each other around the 111_(β1)axis of theirβ_(1)parent phase.The{111}_(β1)crystallographic planes can provide four sets of sublattices with the same orientation for an initial nucleation ofβlattice.It leads to the formation of four translationalβdomains(β_(TA),β_(TB),β_(TC)andβ_(TD)),among which any two differ by a vector of 1/6112_(β1).We deduce theoretically that there exist twenty-fourβdomains during this transition.However,considering the interfacial misfit,only one-third of domains can grow up and eventually formsβribbon.Furthermore,a majority ofβribbons overlap partiallyβ_(1)plate,which is beneficial to relax interfacial strain amongβ,β_(1)andα-Mg matrix(α/β/β_(1)).The configuration of multipleβdomains can effectively regulate interfacial misfit ofα/βandβ/β_(1),which are responsible for enhancing the hardness and strength of Mg-Ce alloy.Additionally,this study aims to provide some clues to improve the over-aged performance of magnesium alloys by constructingβdomains and optimizing theα/β/β_(1)interface.
基金Supported by the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)the center of excellence in vivo molecular imaging research+3 种基金KU Leuven projects IOF-HB/08/009 and IOF-HB/12/018the European Union(AsiaLink Cf P 2006-Europe Aid/123738/C/ACt/Multi-Proposal No.128-498/111)the National Natural Science Foundation of China,No.81071828the Jiangsu Provincial Natural Science Foundation,No.BK2010594
文摘Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research.
文摘Translational Chinese medicine is one of the latest developing fields in traditional Chinese medicine. In this paper, we discuss the “3 w” namely, “what is”, “why to advance”, “how to carry out” and the significance of translational Chinese medicine. To overcome the innate drawbacks of traditional Chinese medicine (TCM), the basic theory of TCM had better be refreshed. The safety and efficacy of classic formulae and therapy experience of TCM should be evaluated based on strict quality control and reaffirmed with evidence based medicine. The significance of translational Chinese medicine is to transform Chinese medicine into a balanced, personalized medicine with sound safety, good efficacy and strict quality control.
文摘In a dynamic CT, the acquired projections are corrupted due to strong dynamic nature of the object, for example: lungs, heart etc. In this paper, we present fan-beam reconstruction algorithm without position-dependent backprojection weight which compensates for the time-dependent translational, uniform scaling and rotational deformations occurring in the object of interest during the data acquisition process. We shall also compare the computational cost of the proposed reconstruction algorithm with the existing one which has position-dependent weight. To accomplish the objective listed above, we first formulate admissibility conditions on deformations that is required to exactly reconstruct the object from acquired sequential deformed projections and then derive the reconstruction algorithm to compensate the above listed deformations satisfying the admissibility conditions. For this, 2-D time-dependent deformation model is incorporated in the fan-beam FBP reconstruction algorithm with no backprojection weight, assuming the motion parameters being known. Finally the proposed reconstruction algorithm is evaluated with the motion corrupted projection data simulated on the computer.
文摘Sound pressure waves surround individuals in everyday life and are perceived by animals and humans primarily through sound or vibration. When sound pressure waves traverse through a solid medium, vibration will result. Vibration has long been considered an unwanted variable in animal research and may confound scientific endeavors using animals. Understanding the characteristics of vibration is required to determine whether effects in animals are likely to be therapeutic or result in adverse biological effects. The eighth edition of the "Guide for the Care and Use of Laboratory Animals" highlights the importance of considering vibration and its effects on animals in the research setting, but knowledge of the level of vibration for eliciting these effects was unknown. The literature provides information regarding therapeutic use of vibration in humans, but the range of conditions to be of therapeutic benefit is varied and without clarity. Understanding the characteristics of vibration(eg, frequency and magnitude) necessary to cause various effects will ultimately assist in the evaluation of this environmental factor and its role on a number of potential therapeutic regimens for use in humans. This paper will review the principles of vibration, sources within a research setting, comparative physiological effects in various species, and the relative potential use of vibration in the mouse as a translational research model.
基金supported by the National Natural Science Foundation of China(Grant No.81725024).
文摘As a major medical and scientific problem perplexing mankind,cardiovascular disease seriously endangers human health and life safety,which is still the primary cause of death.Traditional Chinese medicine(TCM)plays an irreplaceable role in the prevention and treatment of cardiovascular diseases and has its own characteristics and definite advantages.However,the unclear mechanism hinders its further promotion,which is not conducive to the prevention and treatment of cardiovascular diseases.Translational medicine advocates interdisciplinary integration and cooperation between academic groups,to establish effective interaction between basic research and clinical application,lead more medical research to focus on the prevention and treatment of clinical diseases,as well as to accelerate the transformation from“discovery”to“realization”,and finally to benefit patients,that is,“from clinic and serve clinic”.This provides a reference mode for the development and research direction of TCM,which comes from clinical practice originally.Based on this,considering the important role of angiogenesis in the occurrence and prognosis of cardiovascular diseases,under the guidance of the concept of translational medicine,this manuscript sorts out the overview of TCM treatment on angiogenesis related cardiovascular diseases from four aspects:theoretical basis,pathogenesis and pathology,applied prescriptions and material basis,in order to summarize the translational medicine experience of TCM prevention and treatment from clinical practice to modern research,to provide a basis for basic research and clinical diagnosis and treatment of related diseases.
